CN110577529A - Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof - Google Patents

Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof Download PDF

Info

Publication number
CN110577529A
CN110577529A CN201910958291.8A CN201910958291A CN110577529A CN 110577529 A CN110577529 A CN 110577529A CN 201910958291 A CN201910958291 A CN 201910958291A CN 110577529 A CN110577529 A CN 110577529A
Authority
CN
China
Prior art keywords
aryl
hetero
azaindole
reaction
alpha
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201910958291.8A
Other languages
Chinese (zh)
Inventor
田岩
黄一波
孔宪强
吴朝华
吴芳珍
吴长州
孙晓冉
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Changzhou Vocational Institute of Engineering
Original Assignee
Changzhou Vocational Institute of Engineering
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Changzhou Vocational Institute of Engineering filed Critical Changzhou Vocational Institute of Engineering
Priority to CN201910958291.8A priority Critical patent/CN110577529A/en
Publication of CN110577529A publication Critical patent/CN110577529A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Abstract

The invention discloses an alpha-ketone compound containing N- (hetero) aryl-7-azaindole and a preparation method thereof, the invention provides a series of alpha-ketone derivative compounds of N- (hetero) aryl-7-azaindole with novel structures, the variety of the N- (hetero) aryl-7-azaindole derivative compounds is expanded, and the compounds have potential application values in the fields of scientific research, medical treatment, industry and the like; the preparation method has the advantages of good reaction selectivity, yield of over 78 percent, short reaction route, safe and easily controlled reaction process, and small influence on the environment due to the recycling of the catalyst.

Description

Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to an alpha-ketone compound of N- (hetero) aryl-7-azaindole and a preparation method thereof.
Background
7-azaindole is a very important heterocyclic structure, widely exists in bioactive molecules and novel synthetic materials, and widely exists in various anti-tumor, antibacterial and anti-inflammatory drug molecules on the market, such as anti-cancer drug Vemurafenib (Nat. Rev. drug Discovery2012,11,91.), hNK1 receptor (J.bioorg.Med.chem.Lett.2001,11,1233.), potent anti-melanoma agent PLX4720(J.bioorg.Med.chem.Lett.2012,22,789) and the like. The bioactive molecules, synthetic materials and drug molecules are all obtained by derivatization of 7-azaindole, so that the preparation of 7-azaindole derivatives becomes a research hotspot of chemists.
In recent years, derivatization of 7-azaindoles by metal catalysis has been reported. Among them, 7-azaindole is typically used as a guide group, and rhodium, iridium or ruthenium is used for catalyzing to realize selective C-H bond chlorination reaction (org.Lett.2014,16,5294), C-H bond cyanation reaction (J.org.chem.2016,81,6525), C-C bond coupling alkynylation reaction (org.Biomol.chem.2016,14,2944) and C-C bond coupling olefination reaction (org.Biomol.chem.2016,14,229) of N- (hetero) aryl-7-azaindole (the specific derivatization reaction formula is shown in figure 1).
In summary, the types of derivative compounds of N- (hetero) aryl-7-azaindole are rare at present, and the synthesis processes of the derivative compounds all need to use very expensive catalysts, so that the production cost of the N- (hetero) aryl-7-azaindole derivative compounds is high, and therefore, the research and development of novel derivative compounds of N- (hetero) aryl-7-azaindole and preparation methods thereof are of great significance.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, provides an alpha-ketone compound containing N- (hetero) aryl-7-azaindole and a preparation method thereof, provides a series of alpha-ketone derivative compounds of N- (hetero) aryl-7-azaindole with novel structures, expands the variety of the N- (hetero) aryl-7-azaindole derivative compounds, has potential application value in the fields of scientific research, medical treatment, industry and the like, and has the advantages of good reaction selectivity, yield of over 78 percent, short reaction route, safe and easily controlled reaction process and small influence of catalyst recycling on environment.
alpha-ketones of N- (hetero) aryl-7-azaindoles of the formula:
The R is1Is halogen, CF3One of an alkyl group, an alkoxy group or an ester group; the R is1Is aryl or alkyl.
in order to facilitate the smooth preparation of the α -ketone compound of N- (hetero) aryl-7-azaindole, a method for preparing the α -ketone compound of N- (hetero) aryl-7-azaindole is proposed, wherein the α -ketone compound of N- (hetero) aryl-7-azaindole is synthesized by catalysis by using N- (hetero) aryl-7-azaindole and α -carbonylsulfonium ylide as raw materials, metal rhodium, iridium or ruthenium as a catalyst, alkali metal inorganic salt as a reaction additive, and DMF as a solvent.
Preferably, the synthesis reaction temperature is 80-100 ℃, and the reaction time is 10-12 h.
Preferably, the molar ratio of the N- (hetero) aryl-7-azaindole to the alpha-carbonylsulfonium ylide to the catalyst to the reaction additive is 1: 2-5: 0.01-0.05: 1-3.
Preferably, the reaction starting concentration of the N- (hetero) aryl-7-azaindole is 0.1mol/L to 0.3 mol/L.
Preferably, the reaction additive is an alkali metal carbonate or an alkali metal acetate.
The invention has the advantages and beneficial effects that:
the invention provides a series of alpha-keto derivative compounds of N- (hetero) aryl-7-azaindole with novel structures, expands the variety of N- (hetero) aryl-7-azaindole derivative compounds, and has potential application value in the fields of scientific research, medical treatment, industry and the like; the preparation method has the advantages of good reaction selectivity, yield of over 78 percent, short reaction route, safe and easily controlled reaction process, and small influence on the environment due to the recycling of the catalyst.
Drawings
FIG. 1 is a prior art derivatization scheme for 7-azaindoles;
FIG. 2 is a structural formula of an α -keto compound of N- (hetero) aryl-7-azaindole;
FIG. 3 shows the structural formula and yield of α -ketones of N- (hetero) aryl-7-azaindole;
FIG. 4 is a specific synthetic route for α -ketones of N- (hetero) aryl-7-azaindole.
Detailed Description
The following description of the embodiments of the present invention will be made with reference to the accompanying drawings. The following examples are only for illustrating the technical solutions of the present invention more clearly, and the protection scope of the present invention is not limited thereby.
as shown in fig. 2, the structural formula of the alpha-ketone compound of the N- (hetero) aryl-7-azaindole is as follows:
The R is1Is halogen, CF3One of an alkyl group, an alkoxy group or an ester group; the R is1The specific structural formula of the alpha-ketone compound of the N- (hetero) aryl-7-azaindole is shown in figure 3.
in order to facilitate the smooth preparation of the α -ketone compound of N- (hetero) aryl-7-azaindole, a method for preparing the α -ketone compound of N- (hetero) aryl-7-azaindole is proposed, wherein N- (hetero) aryl-7-azaindole and α -carbonylsulfonium ylide are used as raw materials, metal rhodium, iridium or ruthenium is used as a catalyst, alkali metal inorganic salt is used as a reaction additive, DMF is used as a solvent, and the α -ketone compound of N- (hetero) aryl-7-azaindole is synthesized through catalysis, and a specific synthetic route is shown in fig. 4.
example 1
Preparation of 2- (2- (1H-pyrrolo [2,3-b ] pyridin-1-yl) phenyl) -1- (3-chlorophenyl) ethan-1-one (Compound 3 b):
taking 39mg (0.2mmol) of 1-phenyl-1H-pyrrolo [2,3-b ] pyridine, 92mg (0.4mmol) of 1- (3-chlorophenyl) -2- (dimethyl (oxo) -sulfanyl) ethane-1-ketone, 5mg (0.04mmol) of metal rhodium catalyst and 65mg (0.2mmol) of cesium carbonate, dissolving in 3mL of DMF solvent, stirring at 80 ℃ for 12H, adding water and ethyl acetate for extraction, drying the organic phase with anhydrous sodium sulfate, and carrying out column chromatography purification on the crude product obtained by concentrating the organic phase to obtain 57mg of yellow oily liquid (compound 3b), the yield is 83%, and the nuclear magnetic data are shown in figure 3 and are as follows:
1H NMR(400MHz,Chloroform-d)δ8.29(dd,J＝4.8,1.6Hz,1H),7.89(dd,J＝7.9,1.6Hz,1H),7.55(t,J＝1.9Hz,1H),7.48–7.34(m,6H),7.23–7.16(m,2H),7.07(dd,J＝7.8,4.7Hz,1H),6.52(d,J＝3.6Hz,1H),4.14(s,2H).13C NMR(100MHz,Chloroform-d)δ196.17,147.83,143.69,137.88,137.33,134.64,133.03,132.85,131.63,129.63,129.56,129.13,128.77,128.66,128.37,128.06,126.09,120.58,116.41,101.36,41.79.HRMS(ESI+):Calcd.for C21H16ClN2O+[M+H]+:m/z 347.0946；found:347.0945。
Example 2
Preparation of 2- (2- (1H-pyrrolo [2,3-b ] pyridin-1-yl) -5- (trifluoromethyl) phenyl) -1-phenylethane-1-one (compound 3 o):
53mg (0.2mmol) of 1- (4- (trifluoromethyl) phenyl) -1H-pyrrolo [2,3-b ] pyridine, 79mg (0.4mmol) of 2- (dimethyl (oxo) -sulfanyl) -1-phenylethane-1-one, 5mg (0.04mmol) of a metal rhodium catalyst and 16.4mg (0.2mmol) of sodium acetate are dissolved in 3mL of DMF solvent and stirred at 80 ℃ for 10H, water and ethyl acetate are added for extraction, the organic phase is dried over anhydrous sodium sulfate, and the crude product obtained by concentrating the organic phase is purified by column chromatography to obtain 61mg of yellow oily liquid (compound 3o) with yield of 80%, and the nuclear magnetic data thereof are shown in FIG. 3, and the results are as follows:
1H NMR(400MHz,Chloroform-d)δ8.28(dd,J＝4.8,1.6Hz,1H),7.89(dd,J＝7.9,1.6Hz,1H),7.71(dd,J＝5.5,2.4Hz,2H),7.67–7.59(m,2H),7.54–7.44(m,2H),7.31(t,J＝7.8Hz,2H),7.24(t,J＝3.8Hz,1H),7.08(dd,J＝7.9,4.7Hz,1H),6.53(d,J＝3.6Hz,1H),4.28(s,2H).13C NMR(151MHz,Chloroform-d)δ196.44,147.76,143.82,140.69,136.10,134.18,133.28,129.36,129.18,129.14,129.11,129.08,128.47,127.92,125.28,125.25,120.71,116.72,102.07,41.78.HRMS(ESI+):Calcd.for C22H16F3N2O+[M+H]+:m/z 381.1209；found:381.1207。
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the technical principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (6)

  1. An α -keto compound of N- (hetero) aryl-7-azaindole having the structural formula:
    The R is1is halogen, CF3One of an alkyl group, an alkoxy group or an ester group; the R is1is aryl or alkyl.
  2. A process for producing an α -keto compound of N- (hetero) aryl-7-azaindole according to claim 1, which comprises catalytically synthesizing an α -keto compound of N- (hetero) aryl-7-azaindole from N- (hetero) aryl-7-azaindole and α -carbonylsulfonium ylide as raw materials, rhodium, iridium or ruthenium as a catalyst, an alkali metal inorganic salt as a reaction additive, and DMF as a solvent.
  3. 3. The method for preparing an α -ketone compound of N- (hetero) aryl-7-azaindole according to claim 2, wherein the synthesis reaction temperature is 80 to 100 ℃ and the reaction time is 10 to 12 hours.
  4. 4. The method for producing an α -ketone compound of N- (hetero) aryl-7-azaindole according to claim 3, wherein the molar ratio of N- (hetero) aryl-7-azaindole to α -carbonylsulfonium ylide to the catalyst to the reaction additive is 1:2 to 5:0.01 to 0.05:1 to 3.
  5. 5. The method for producing an α -keto compound of N- (hetero) aryl-7-azaindole according to claim 4, wherein the reaction starting concentration of N- (hetero) aryl-7-azaindole is 0.1mol/L to 0.3 mol/L.
  6. 6. The process for preparing α -keto compounds of N- (hetero) aryl-7-azaindole of claim 5, wherein the reaction additive is an alkali metal carbonate or an alkali metal acetate.
CN201910958291.8A 2019-10-10 2019-10-10 Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof Pending CN110577529A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910958291.8A CN110577529A (en) 2019-10-10 2019-10-10 Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910958291.8A CN110577529A (en) 2019-10-10 2019-10-10 Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof

Publications (1)

Publication Number Publication Date
CN110577529A true CN110577529A (en) 2019-12-17

Family

ID=68814516

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910958291.8A Pending CN110577529A (en) 2019-10-10 2019-10-10 Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof

Country Status (1)

Country Link
CN (1) CN110577529A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113045530A (en) * 2021-03-23 2021-06-29 成都大学 Method for preparing naphthopyran compounds by ruthenium catalysis

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108003086A (en) * 2017-11-15 2018-05-08 宁波大学 A kind of preparation method of 3- amidos -2- indole ketone compounds

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108003086A (en) * 2017-11-15 2018-05-08 宁波大学 A kind of preparation method of 3- amidos -2- indole ketone compounds

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHANG YOU ET AL.: ""Rh(III)-Catalyzed Selective C8-H Acylmethylation of Quinoline N-Oxides"", 《ADVANCED SYNTHESIS & CATALYSIS》 *
SHUAI-SHUAI LI ET AL.: ""One-pot construction of fused polycyclic heteroarenes involving 7-azaindoles and α,β-unsaturated ketones"", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 *
SHUYING JI ET AL.: ""Cp-Co(III)-Catalyzed C-H Acylmethylation of Arenes by Employing Sulfoxonium Ylides as Carbene Precursors"", 《ORGANIC LETTERS》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113045530A (en) * 2021-03-23 2021-06-29 成都大学 Method for preparing naphthopyran compounds by ruthenium catalysis
CN113045530B (en) * 2021-03-23 2024-04-09 成都大学 Method for preparing naphthopyran compounds by ruthenium catalysis

Similar Documents

Publication Publication Date Title
CN107382856B (en) Novel polysubstituted isoquinoline derivative and synthetic method thereof
CN105801575B (en) A kind of synthetic method of imidazo [1,2-a] pyridine
CN108863890B (en) 4-pyrroline-2-ketone derivative and preparation method thereof
CN108864147B (en) Octanitrogen oxygen heterocyclic spiro indolone compound and preparation method thereof
CN110577529A (en) Alpha-ketone compound of N- (hetero) aryl-7-azaindole and preparation method thereof
CN108864164B (en) Synthesis method of primary amine-guided 2-alkynyl indole compound
CN113087667B (en) Synthesis method of imidazolidinone derivative
JP6067700B2 (en) Alcohol oxidation catalyst and alcohol oxidation method using the same
CN111777564B (en) Method for synthesizing quinazolinone compound by photocatalytic alcohol oxidation in aqueous phase
CN110028451A (en) A kind of full substituted pyrazole derivative preparation method
CN113880781B (en) Method for synthesizing 3-trifluoromethyl substituted 1,2, 4-triazole compound by taking glucose as carbon source
CN105272987A (en) Preparation method of 3-cyano-N-confused porphyrin compound
EP3307717B1 (en) A novel process for preparing enzalutamide
CN104774202A (en) Synthesis method of 9H-pyridino[2,3-b]indole compounds
CN111362795B (en) Preparation method of substituted butyrate derivatives
CN114989063A (en) Synthesis method of beta-halopyrrole compound
CN108929251B (en) Method for direct trifluoromethylation of C (sp3) -H
CN103848830A (en) Simple method for synthesizing imidazo (1,2-a) pyridine derivatives
CN110357879B (en) Preparation method of C-3 benzyl indolizine compound
CN111718301B (en) Synthetic method of quinazolinone derivative
CN111995543B (en) Synthetic method of alpha-ketoamide compound
CN111517903B (en) Aromatic C-NO catalyzed by transition metal 2 Hiyama coupling method of
CN112125843B (en) Preparation method of 3-hydroxymethyl-4-phenyl-3, 4-dihydroquinolinone compound
JP5208928B2 (en) C2-ruthenocene bisphosphine ligand having only symmetric planar chirality and its synthesis method
CN113234083B (en) Tetrahydroquinoline pyran compound and preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20191217

RJ01 Rejection of invention patent application after publication